Title:Potential Impact of Genetic Variants in Nrf2 Regulated Antioxidant Genes and Risk Prediction of Diabetes and Associated Cardiac Complications
VOLUME: 20 ISSUE: 37
Author(s):T. Ramprasath and G. S. Selvam
Affiliation:Molecular Cardiology Unit, Department of Biochemistry, Center for Excellence in Genomic Sciences, School of Biological Sciences, Madurai Kamaraj University, Madurai 625021, Tamilnadu, India.
Keywords:Cardiovascular disorders, diabetes, GPx-1, GST, NQO1, Nrf2/ARE.
Abstract:The prevalence, incidence and mortality of all cardiovascular disorders (CVD) are two- to eightfold higher in
persons with diabetes than in those without diabetes. Predicting and understanding the causes of CVD still represents an
enormous challenge for clinical and basic cardiovascular science. Similarly, the fundamental mechanism by which diabetic
patients are more prone to heart failure is unclear and prevention of such cardiac risk remains a major challenge for
which new strategies are needed. Imbalance between free radicals and anti-oxidant defenses is associated with cellular
dysfunctions leading to the pathophysiology of various diseases. Evidence suggests that diabetes is associated with a reduced
overall antioxidant defense system and the increased oxidative stress. This may contribute to the pathogenesis of
the diabetic complications, notably the emergence of premature atherosclerosis. The transcription factor NF-E2-related
factor 2/antioxidant response element (Nrf2/ARE) regulates the expression of many detoxifying genes such as catalase,
superoxide dismutase, UDP-glucuronosyltransferase, c-glutamylcysteine synthetase, NAD(P)H quinone oxidoreductase 1,
glutathione- S-transferase, glutathione peroxidase-1 and heme oxygenase-1. Polymorphic effects of these antioxidant
genes and their regulatory regions have higher relevancy to the susceptibility to clinical conditions such as diabetes, obesity
and cardiovascular diseases. Thus, the present review aims to explore the relationship between free radicals, diabetes
and its associated complications with respect to the genetic makeup of Nrf2/ARE regulated genes in an effort to expand
treatment options.
